Conventionally, various attempts to evaluate genetic activity or decode biological processes, such as a disease process or a biological process of pharmacological effect, have been focused on genomics. However, proteomics can provide more detailed information about the biological function of cells. Proteomics includes qualitative and quantitative measurement of gene activity by detecting and quantifying expressions at the level of proteins rather than the level of genes. Proteomics also includes studies of events which are not coded to genes, such as a post-translational modification of protein and an interaction between proteins.
At present, an enormous volume of genome information has been able to be gained. Accordingly, for researches on proteomics, rapidness and high efficiency (high throughput) have been increasingly demanded. DNA chips have been come into practical use as molecular arrays for this purpose. On the other hand, in order to detect proteins which are the most complicated and the most variable in biological functions, there are proposed protein chips, which are enthusiastically studied in these days. A protein chip is a collective term used to refer to any device in which a protein or a molecule for catching a protein is fixed on a surface of a chip (a fine substrate or particle).
At present, protein chips are generally developed as an extension of DNA chips. Therefore, attempts are made for fixing a protein or a molecule for catching such a protein, into a spot form, onto a surface of a chip such as a glass substrate (see, e.g., Patent Document 1). For example, the fixation of a protein by physical absorption thereof, and others are performed. In such a protein chip, it is preferred that high signals are outputted therefrom; thus, a chip having a high capability of fixing a protein or a molecule for catching it onto a surface of a chip is being desired.
In the meantime, in the detection of signals from a protein chip, a cause of lowering the signal to noise ratio is nonspecific adsorption of a target substance to be detected onto a substrate (see, e.g., Non-Patent Document 1).
In the above-mentioned fixation of a protein by physical adsorption thereof, adsorption preventing agents are coated in order to prevent nonspecific adsorption of a secondary antibody after the protein is fixed. However, the ability of these agents for preventing the nonspecific adsorption is not sufficient. Moreover, the biochip is coated with the adsorption preventing agent after a primary antibody is fixed; therefore, there is caused a problem that the fixed protein is coated so that the reactivity with the secondary antibody deteriorates. For this reason, there is a need for a biochip capable of decreasing the nonspecific adsorption amount of a biologically active substance without being coated with any adsorption preventing agent after a primary antibody is fixed.
In order to decrease the nonspecific adsorption amount of a biologically active substance onto a biochip, it is effective to improve the hydrophilicity of the biochip. However, in the case that such a biochip is used, since the chip has a high hydrophilicity, there is a problem that the protein or the molecule for catching the protein which is fixed on the substrate flows out in the washing process after the protein is caught, so that the signals therefrom decrease. As one approach to this problem, there is disclosed a method of coating a supporting substrate with an active component containing a functional group, a spacer group and a bonding group, a cross-linking component and a matrix-forming component and then curing them, whereby a functional surface strongly bonded with the upper of the supporting substrate can be formed (e.g. Patent Document 2). However, in this disclosed method, although the curing of low molecular components advances on the supporting substrate, the curing reaction involves a shrinkage in the volume of the reactants, so that the supporting substrate may be warped or deformed if the supporting substrate is a plastic substrate. Moreover, a matrix in the form of a network is formed, so as to cause problems that the reaction of the functional group for fixing a biologically active substance may be adversely restricted, and that the reproducibility of the functional expression of the fixed biologically active substance is poor. Furthermore, even if the chip is washed, the protein infiltrated into the inside of the matrix is not completely removed. Thus, there also remains a problem that the nonspecific adsorption cannot be inhibited sufficiently.    Patent Document 1: Japanese Patent Application Laid-Open No. 2001-116750.    Patent Document 2: Japanese Patent Application National Publication (Laid-Open) No. 2004-531390.    Non-Patent Document 1: Hayashizaki, Y. and Okazaki, K., 2000, “Practical Manual of DNA Microarray”. P. 57, Yodosha Co., Ltd., Tokyo.